1. Field of the Invention
The present invention relates to a process for preparing L-.alpha.-methylphenyl alanines by biochemical asymmetric hydrolysis of DL-.alpha.-methylphenyl alanine amides, in which a microbial enzyme catalyzing a hydrolysis of L-isomer of DL-.alpha.-methylphenyl alanine amides is utilized.
2. Description of the Prior Art
It is known in the art that pharmacological activities are possessed by L-.alpha.-methylphenyl alanines, but not D-.alpha.-methylphenyl alanines. For instance, L-3,4-dihydroxy-.alpha.-methylphenyl alanine, usually referred to as "methyl dopa", is a well-known excellent hypotensor, while D-3,4-dihydroxy-.alpha.-methylphenyl alanine has no hypotensor activity. Accordingly, effective optical resolution of chemically synthesized DL-.alpha.-methylphenyl alanines is an extremely important problem to be solved in the art.
Various optical resolution methods of the racemic mixture of .alpha.-methylphenyl alanines have been heretofore proposed, including physical methods, such as diastereomer methods or fractional crystallization methods, and biochemical methods, utilizing microorganisms.
Diastereomer methods are disadvantageous in that the yield of the desired product is low, the recovery of the desired product is troublesome, the resolution agent used is expensive, and the recovery of the resolution agent is not easy.
Fractional crystallization methods are disadvantageous in that the racemic mixture is often crystallized prior to crystallization of the desired optically active product even if crystals of the desired optically active product are seeded and that both the resolution rate (%) and the crystallization reproducibility of the desired optically active product are low.
In known biochemical resolution methods, N-succinyl or N-benzoyl derivatives of DL-.alpha.-methylphenyl alanines are used as substrates for asymmetric hydrolysis by microbial enzymes. These methods are, however, disadvantageous in that the synthesis of the substrates is troublesome, the reuse of the remaining substrates (i.e., D-derivatives) is difficult, and the yield of the desired product is low.